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One key information of the HEp-2 IFA test is the immunofluorescence pattern, which indicates the possible location of the autoantigens recognized by the autoantibodies in the sample. The indirect immunofluorescence assay on HEp-2 cells (HEp-2 IFA) is the most commonly used method for screening for autoantibodies in systemic autoimmune diseases, including SSc. In general, anti-fibrillarin antibodies indicate worse prognosis in SSc patients. Although there are not many studies, anti-fibrillarin has been associated with dcSSc and multi-organ involvement, with high risk of cardiac involvement, ILD, PAH, renal crisis, small bowel and muscle involvement. Anti-fibrillarin occurs in up to 10% of SSc patients, especially in African-Americans. Īnti-U3-RNP/fibrillarin antibodies recognize the U3-ribonucleoprotein (U3-RNP), a nucleolar complex involved in pre-rRNA processing. In contrast, anti-centromere antibodies are associated with lcSSc, long-standing Raynaud’s phenomenon, calcinosis, a higher risk of developing pulmonary arterial hypertension (PAH), and better survival rates as compared with patients with anti-topo I and anti-RNAP III antibodies. Anti-RNA polymerase III (RNAP III) antibodies are associated with the dcSSc subset, high risk of severe, rapidly progressing cutaneous thickening, higher risk for gastric antral vascular ectasia, and scleroderma renal crisis, as well as a higher risk of development of malignancy, especially within the first years of disease onset.
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For example, anti-topoisomerase I antibodies are associated with dcSSc, digital ulcers, cardiomyopathy, high skin score, higher risk of severe interstitial lung disease (ILD) and underlying malignancies, resulting a more severe phenotype and increased mortality. Several of these autoantibodies are highly specific for SSc and help predicting clinical complications and the prognosis of SSc patients. Serum autoantibodies can be detected in over 90% of SSc patients and are very useful for the early diagnosis of SSc and for the identification of certain SSc disease phenotypes. In contrast, patients with lcSSc typically have restricted skin thickening distribution, less severe organ involvement and a better survival.
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Patients with dcSSc have rapidly diffuse cutaneous thickening, higher frequency of internal organ involvement, and worse prognosis. The heterogeneity of the disease may be represented by the subset classification of SSc, i.e., the limited (lcSSc) and diffuse cutaneous subsets (dcSSc). However, the clinical manifestations and the clinical course of the disease are highly variable. SSc has the highest morbidity and mortality rates among immune-mediated rheumatic diseases. Systemic sclerosis (SSc) is a chronic heterogeneous systemic autoimmune disease characterized by microvascular dysfunction, activation of the immune system, and cutaneous and visceral fibrosis.